Project Abstract The overall objective of this research plan is to develop a small endoscopic therapeutic ultrasound phased array integrated within a deployable acoustic reflector balloon, which once inserted via mouth into the stomach, expands to mimic a larger aperture HIFU phased array which can produce deeper, more localized, and tailored thermal/acoustic therapy directly and more effectively to treat pancreatic tumors. For advanced-stage pancreatic cancer patients (~80% at diagnosis), tumor down-staging, prolongation of survival, and palliative relief of symptoms are the major clinical goals, with chemotherapy and radiotherapy most commonly applied. Thermal ablation and hyperthermia therapies are minimally-invasive treatment alternatives with potential to provide similar or better clinical benefit with less complications and expense, but techniques for delivery to pancreatic tumors are inadequate. Extracorporeal image-guided HIFU can precisely deliver thermal and/or acoustic therapy to treat pancreatic tumors; however, significant limitations to patient candidacy and complications arise due to challenging and limited tumor accessibility from external application. Supportive work by our group has demonstrated the feasibility of targeting pancreas from within the stomach using endoluminal ultrasound devices under MR guidance, but due to size constraints on the transducer the penetration depth and localization was limited to ~2.5 cm deep ablation zones contiguous with the stomach. Additionally, conical-shaped reflective balloons over a tubular transducer, in combination with a perfluorocarbon fluid lens of variable distention, could produce deep focusing in tissue, however dynamic control of the focus requires manipulation of lens fluid volume and can be sensitive to distention/compression. In response, we propose an innovative endoluminal device, with a tubular ultrasonic phased array integrated within a custom shaped expandable reflector balloon, which allows for compact device delivery through a constrained body lumen and deployment at a treatment site, where the reflector balloon is expanded to increase the effective aperture (emulating a larger concentric-ring/sector- vortex HIFU transducer). Incorporation of a tubular phased array provides an effective means of modulating the ultrasound beam focal depth and width electronically for precision control and dynamic adjustability over the 3D energy localization. The goals of this project are: (1) to develop low-profile ultrasound phased array applicators integrated within deployable reflector assemblies specific for endoluminal thermal therapy of the pancreas; (2) to implement computer simulations for phased array design, reflector balloon geometries, delivery strategies, and performance evaluation; and (3) to perform in vivo experimental evaluation of the deployable ultrasound phased array applicator under MR guidance for ablation and hyperthermia of pancreatic tissue in a swine model. Completion of this proposed study has potential to lead to a novel and accurate minimally-invasive method for spatially selective treatment of pancreatic cancer with thermal or acoustic therapy, with discretion to avoid damage to non-target tissues, and can be used alone or as a powerful adjunct to other therapies.